高效液相色谱-质谱联用法在头孢唑肟钠中基因毒性杂质控制的应用  

Application of High Performance Liquid Chromatography-Tandem Mass Spectrometry for the Control of Genotoxic Impurity in Ceftizoxime Sodium

作　　者：亓恒芹 吕远 孟龙 韩勇 孔令洋 王冉 QI Hengqin;LV Yuan;MENG Long;HAN Yong;KONG Lingyang;WANG Ran(Pharmacy Department,Jining Dermatosis Prevention and Control Hospital,Shandong Jining 272100,China;Jining Institute for Food and Drug Control,Shandong Jining 272071,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]济宁市皮肤病防治院药剂科,山东济宁272100 [2]济宁市食品药品检验检测研究院,山东济宁272071 [3]中国中医科学院中药研究所,北京100700

出　　处：《中国医药导刊》2023年第6期570-574,共5页Chinese Journal of Medicinal Guide

基　　金：山东省市场监督管理局2021年科研项目(项目编号:202102;项目名称:AE活性酯合成的头孢类抗生素中基因毒性杂质的研究与控制)。

摘　　要：目的:建立高效液相色谱-质谱联用法(LC-MS/MS)测定头孢唑肟钠中基因毒性杂质2-巯基苯并噻唑(MBT)的含量。方法:采用Waters BEH C 18色谱柱(50 mm×2.1 mm,1.7μm),以0.01 mol·L^(-1)乙酸铵溶液-乙腈为流动相,梯度洗脱,流速为0.3 mL·min^(-1),柱温为30℃,自动进样器温度4℃,进样体积为10μL。质谱检测器采用电喷雾离子源(ESI),在正离子多反应监测(MRM)模式下通过对定量子离子(质荷比168→135)扫描测定MBT。结果:MBT在浓度2.9607~394.7640 ng·mL^(-1)范围呈良好的线性关系(r=0.9999);平均回收率为95.05%,RSD为1.53%(n=9)。结论:本方法专属性强、准确、灵敏且耐用性良好,适用于测定头孢唑肟钠中MBT含量,为该产品临床应用安全提供保障。Objective:To establish a method for the determination of genotoxic impurity 2-mercaptobenzothiazole(MBT)in ceftizoxime sodium by high performance liquid chromatography-tandem mass spectrometry(LC-MS/MS).Methods:The chromatography was performed on Waters BEH C 18 column(50 mm×2.1 mm,1.7μm)with a mobile phase of 0.01 mol·L^(-1)ammonium acetate-acetonitrile by gradient elution at a flow rate of 0.3 mL·min-1.The column temperature was 30℃.The autosampler temperature was 4℃,and the injection volume was 10μL.Meanwhile,the positive ion multiple reaction monitoring(MRM)mode was used with electron spray ionization(ESI)as the ion source,and the quantitative transition of MBT was m/z 168→135.Results:The concentration of MBT had good linear relationship with its chromatographic peak area within the range of 2.9607-394.7640 ng·mL^(-1)(r=0.9999).The average recovery rate was 95.05%(n=9),and the RSD value was 1.53%(n=9).Conclusion:The method has strong specificity,accuracy,sensitivity,and good durability,which can be used for the determination of MBT content in ceftizoxime sodium,and provides a guarantee for the safety of clinical application of the product.

关 键 词：头孢唑肟钠 2-巯基苯并噻唑 基因毒性杂质 高效液相色谱-质谱联用法 

分 类 号：R284.1[医药卫生—中药学]